HypoEvolve: Genetic Algorithms Enable Multi-Agent LLMs to Discover Scientific Hypotheses

Scientific agents increasingly contribute to hypothesis discovery by synthesizing evidence, assessing proposals, and developing new explanations. Recent systems bring scientific agents and evolutionary search together to develop hypotheses through cycles of critique, comparison, and revision. However, how different forms of agent collaboration affect hypothesis quality remains an open question. Answering this question requires separating the effects of agents' scientific capabilities from those of their collaboration. A suitable framework must therefore preserve the agents' scientific roles and support different rules for combining, revising, and retaining hypotheses. Building on this perspective, we introduce HypoEvolve, which makes collaboration explicit through successive updates to a hypothesis population. Specifically, we propose to use a generational genetic algorithm to coordinate specialized large language model (LLM) agents that integrate mechanistic arguments, reconsider assumptions, and assess evidence and testability. Each generation specifies how scientific judgments and new proposals reshape the population, which makes the effects of collaboration on hypothesis quality directly testable. Moreover, we design our evaluation around scientifically meaningful hypotheses that explain how a proposed intervention could work. Drug repurposing connects these explanations to target-level biological claims that can be assessed against external evidence. Specifically, we adapt DepMap and Open Targets into complementary external measures grounded in experimental, genetic, and clinical evidence. The evaluation spans 34 cancer types, with HypoEvolve achieving the highest scores against six baselines on both measures. DepMap selectivity reaches 0.171, compared with 0.115 for the strongest baseline. Gains over single-pass generation also generalize to held-out cancer types. HypoEvolve advances a vision of autonomous science in which AI research teams achieve a capacity for discovery beyond that of individual models.